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Thyroid function, adipokines and mitokines in metabolic dysfunction-associated steatohepatitis: A multi-centre biopsy-based observational study.
Kouvari, Matina; Valenzuela-Vallejo, Laura; Axarloglou, Evangelos; Verrastro, Ornella; Papatheodoridis, Georgios; Mingrone, Geltrude; George, Jacob; Mantzoros, Christos S.
Afiliação
  • Kouvari M; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Valenzuela-Vallejo L; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Axarloglou E; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Verrastro O; Università Cattolica del Sacro Cuore, Rome, Italy.
  • Papatheodoridis G; Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
  • Mingrone G; Università Cattolica del Sacro Cuore, Rome, Italy.
  • George J; Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
  • Mantzoros CS; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Liver Int ; 44(3): 848-864, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38263703
ABSTRACT
BACKGROUND AND

AIMS:

Thyroid axis is currently under investigation as a therapeutic target in metabolic dysfunction-associated steatotic liver disease (MASLD). Thyroid function was examined herein in the full spectrum of disease.

METHODS:

Subjects were recruited and had liver biopsies in two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy). The main working sample was n = 677 subjects with MASLD after excluding subjects with abnormal free thyroxine levels. Participants were classified according to thyroid-stimulating hormone (TSH) standard criteria Subclinical hyperthyroidism (<0.4 uIU/mL); Euthyroidism with relatively low (0.4 to <2.5 uIU/mL); euthyroidism with relatively high (2.5-4.0 uIU/mL); subclinical hypothyroidism (>4 uIU/mL).

RESULTS:

TSH as a continuous variable was positively associated with significant fibrosis (F ≥ 2), metabolic dysfunction-associated steatohepatitis (MASH) and at-risk MASH. Subclinical hypothyroidism was associated with fibrosis F ≥ 2 (odds ratio [OR] = 3.47, 95% confident interval [CI] [1.50, 8.05], p = .02), MASH (OR = 3.44, 95% CI [1.48, 7.98] p = .001) and at-risk MASH (OR = 3.88, 95% CI [1.76, 8.55], p = .001), before and after controlling for adiposity, central obesity, and insulin resistance. When leptin, adiponectin, or growth differentiation factor-15 were examined as moderators, significance was lost. Sex-specific analysis revealed a strong association between TSH and the presence of significant fibrosis among women, eliminated only when adipokines/mitokines were adjusted for. Restricted cubic spline analysis revealed associations between TSH and liver outcomes (p-values < .01) with inflection points for fibrosis F ≥ 2 being 2.49, for MASH being 2.67 and for at-risk MASH being 6.96.

CONCLUSIONS:

These observations provide support for studies on the administration of thyroid hormone in MASLD therapeutics for subclinical hypothyroidism and liver-specific thyroid receptor agonists for subjects across the TSH continuum.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fígado Gorduroso / Hipotireoidismo Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fígado Gorduroso / Hipotireoidismo Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Liver Int Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos